crossing96/oncoscreening huggingface dataset:
Managing utilization of new diagnostic tests.	In appropriate utilization of laboratory testing has been estimated to range from 10% to 50% of the volume encountered in hospital laboratories. Many strategies to control utilization of laboratory testing have been reported, including redesigning test requisitions, changing standing orders, the use of provider order entry, physician profiling, and educational initiatives. The major motivation to reduce utilization of unnecessary testing is financial, although other benefits also may be observed, such as reducing false-positive results stemming from testing patients in low prevalence populations, eliminating unnecessary follow-up procedures, avoiding iatrogenic anemia, and potentially lowering hospital length of stay resulting from the need to track down the significance of falsely abnormal tests. The majority of utilization control efforts have focused on reducing routine laboratory tests such as chemistry profiles and automated blood counts. In many hospitals novel diagnostic tests, especially in molecular genetics and oncology, are the major driver behind increasing laboratory costs. Traditional methods to control utilization of routine testing are usually ineffective in controlling testing of novel diagnostic methods. In most cases, test requests originate from a small group of physician specialists who typically are more knowledgeable in their area of expertise than is the clinical pathologist. For this reason, a different approach is generally required. It is particularly important to establish an institutional structure authorized to review and approve new laboratory tests. The clinical pathologist usually takes the lead in this effort because laboratory-based physicians are familiar with new tests being requested by physicians across a spectrum of medical specialties. To be successful, the laboratory physician must identify potential utilization issues, acquire and analyze data, function on interdepartmental teams, and develop strategies to satisfy the needs of clinicians while at the same time preventing introduction of inappropriate technologies into the laboratory. This article will give a perspective on approaches to laboratory test utilization and offer specific examples of initiatives we have undertaken in our institution. The examples will illustrate how the pathologist can use knowledge of medicine and the clinical laboratory in conjunction with organizational and team building skills. In the final analysis, the process is more of an art than a science.	bladder
HER2/neu gene amplification and protein overexpression in G3 pT2 transitional cell carcinoma of the bladder: a role for anti-HER2 therapy?	HER2/neu is an oncogene encoding a type 1 tyrosine kinase growth factor receptor. Polysomy 17, gene amplification and HER2/neu protein overexpression are associated with a poor prognosis in transitional cell carcinomas (TCC) of the bladder. Due to the application of different laboratory techniques, the exact incidence of HER/neu abnormalities remains uncertain in TCC. Standardised laboratory techniques are therefore important in the determination of the HER2/neu status if an assessment of the potential value of anti-HER2/neu treatments in the clinical management of patients with TCC is to be made. In this study, 75 TCCs with evidence of detrusor muscle invasion at first clinical presentation were included. Gene amplification, polysomy 17 and HER2 copy number were assessed using fluorescence in situ hybridisation (FISH), with separate probes for chromosome 17 and HER2/neu. Protein overexpression was assessed using immunohistochemistry (IHC), with the CB11 antibody and a scoring system evaluating only membranous staining as positive. The mean patient age was 69.5 years (range 42-93 years) and the median survival was 15 months (range 1-156 months). Polysomy 17 occurred in 97%, increased HER/neu copy number in 92% and HER2/neu gene amplification in 7%. Protein overexpression occurred in 57% of cases. Polysomy 17 and HER2/neu protein overexpression are common in G3 pT2 TCCs of the bladder. However, gene amplification is uncommon. Mechanisms other than gene amplification may be responsible for protein overexpression in this tumour type. Evidence from breast cancer suggests that only tumours with HER2/neu gene amplification respond to the anti-HER2/neu therapy trastuzumab (Herceptin). If this were true for bladder cancer, only 4/75 (5%) of G3 pT2 TCCs would be suitable for treatment. The role of trastuzumab in these tumours remains untested at present.	bladder
Bladder cancer therapy using combined proliferating cell nuclear antigen antisense oligonucleotides and recombinant adenovirus p53.	OBJECTIVE: To evaluate the antitumor efficacy of proliferating cell nuclear antigen antisense oligonucleotide (PCNA-ASO) in combination with recombinant adenovirus p53 (Ad-p53) against bladder cancer EJ and BIU-87 cells in vitro and in vivo. METHODS: Cells were transfected with Ad-p53 (100 MOI), and PCNA-ASO (1.6 micro mol/L) was then introduced into the cells using a cationic lipid (lipofectamine, 20 micro l/ml). In vitro and in vivo antitumor effects of combining PCNA-ASO with Ad-p53 were measured using the MTT assay, flow cytometry, clone formation, and a nude mice model. RESULTS: The combination of PCNA-ASO and Ad-p53 inhibited cell viability in both the EJ (89.3%) and BIU-87 (78.6%) cell lines. The ability of the cells to form foci was also reduced by 74.8% in EJ cells and by 67.5% in BIU-87 cells (P < 0.01). A significant decrease of cells in the S phase (11.4% in EJ cells, 14.6% in BIU-87 cells) and a significant increase of cells in G1 phase (62.2% in EJ, 56.8% in BIU-87) were noted. The mean tumor volume after 7 days of treatment with PCNA-ASO or Ad-p53 in combination decreased to 47.6% or 36.4% of the initial tumor size in the two cell lines respectively. CONCLUSION: These results indicate that combined PCNA-ASO and Ad-p53 in the treatment of bladder cancer with mutant p53 has important therapeutic potential, significantly suppressing the growth of human bladder cancer both in vitro and in vivo.	bladder
Antitumor effect of a novel nuclear factor-kappa B activation inhibitor in bladder cancer cells.	Nuclear factor (NF)-kappaB is a transcription factor that not only induces and controls various genes, including those of inflammatory cytokines, but also activates genes which suppress apoptosis. It has been clearly demonstrated that certain advanced human bladder cancer cells constitutively acquire the ability to activate NF-kappaB, which not only protects cancer cells from apoptotic cell death, but also upregulates the production of various cytokines that may increase the malignant potential of the disease and cause paraneoplastic syndromes. The NF-kappaB inhibitors may therefore be useful as anticancer agents. An NF-kappaB function inhibitor, a dehydroxymethyl derivative of epoxyquinomicin C (DHMEQ), has recently been designed and synthesized. The effectiveness of DHMEQ against advanced human bladder cancer cell line KU-19-19, in which NF-kappaB is constitutively activated, has been investigated. The DNA-binding activity of NF-kappaB was completely inhibited following 2-6-h exposure to 10 microg/ml of DHMEQ. Marked levels of apoptosis were observed 48 h after DHMEQ administration. These results confirmed that NF-kappaB activation maintains the viability of KU-19-19 cells, that DHMEQ inhibited constitutively activated NF-kappaB, and, consequently, apoptosis was induced. However, it was still possible that DHMEQ caused apoptotic cell death through some other mechanism which has not yet been fully investigated. The authors conclude that DHMEQ could represent a new treatment strategy against advanced bladder cancer.	bladder
Comparison of the nuclear matrix protein 22 with voided urine cytology in the diagnosis of transitional cell carcinoma of the bladder.	Several urinary markers for transitional cell carcinoma have been investigated, including urine cytology, bladder tumor antigen, autocrine motility factor receptor and fibrin degradation products. Unfortunately, they have poor overall sensitivity. The United States Food and Drug Administration have recently approved nuclear matrix protein (NMP 22) for the detection of occult or rapidly recurring disease after transurethral resection of bladder tumor. The objective of the current study was to assess the sensitivity of NMP 22 for the detection of bladder carcinoma, as well as to correlate the NMP 22 values with multiplicity of tumor, tumor size, configuration, stage and grade respectively. A total of 78 patients (38 with bladder cancer) provided a urine sample which was divided into appropriate aliquots for each of urine cytology and NMP 22. Comparative results demonstrate a clear superiority of NMP 22 in bladder cancer detection (52.6% vs 31.6% sensitivity), while specificity was in favor of urine cytology (100% vs 82.5%). For superficial tumors, sensitivity was 78.5% for NMP 22 and 41.6% for cytology and for invasive cancers, sensitivity was 90% for NMP 22 and 60% for cytology. Urinary NMP 22 levels were significantly correlated with tumor grade and were significantly higher in large tumors than small tumors. NMP 22 test results showed sufficient sensitivity in comparison with urine cytology for the detection of transitional cell carcinoma. However, we do not think that it is a useful tool as a substitute for endoscopic examination for the detection and surveillance in bladder cancer.	bladder
[Preliminary results of selective combined therapy for patients with urinary bladder cancer].	The paper discusses the methods of complex treatment for invasive bladder cancer which includes radiation therapy, regional intraarterial chemotherapy with cisplatin drugs, selective hyperglycemia and local SHF-hyperthermia. Complete local response was reported in 18 (56%) out of 32 patients with stage II-IV tumors, partial--8 (25%), no response--6 (19%). The method appeared effective and safe; it offers good perspectives in bladder cancer treatment.	bladder
Urethral wash cytopathology for monitoring patients after cystoprostatectomy with urinary diversion.	BACKGROUND: Urethral wash cytopathology (UWC) has been recommended for monitoring patients after cystoprostatectomy with preservation of the penile urethra and urinary diversion. The rationale has been that early detection of urethral neoplasms (recurrences) would allow for urethrectomy to be performed before an invasive tumor developed and thus prevent or delay disease progression. Negative results of UWC would spare the patient a major surgical procedure. The authors analyzed the clinical and pathologic records of patients undergoing cystoprostatectomy with urinary diversion and preservation of the penile urethra to determine the cytohistologic correlations and to document the effect of UWC monitoring on the rate of disease progression. METHODS: All cases of men undergoing a cystoprostatectomy with urinary diversion and preservation of the penile urethra over a 12-year period at the study institution were included. Records were reviewed to determine the degree of risk associated with the pathologic findings at surgery and to document the presence or absence of disease progression for each individual. The pathologic specimens of all cases monitored with UWC were reviewed separately by both authors to establish cytohistologic correlations. Standard statistical methods were applied. RESULTS: Of 176 patients, urethral recurrence and disease progression occurred in both high-risk and low-risk groups. Among the 48 individuals monitored with UWC, 13 had a positive diagnosis, and 10 of these 13 had been subsequently treated with urethrectomy. Among 128 patients not monitored with UWC, 16 underwent urethrectomy. Patients in both groups had recurrent urethral neoplasms. Most lesions were focal carcinomas in situ occupying the paraurethral glands. One individual in each group had no further disease progression, even though the urethral tumor was invasive. Urethrectomy was found to have no statistically significant association with the rate of disease progression, regardless of whether the procedure resulted from a positive UWC or was provoked by patient/clinician concern. When groups were compared on the basis of monitoring with UWC, there was no statistical difference in the rate of disease progression between those monitored with UWC and those who were not. Within the monitored group, however, the cytopathologic interpretations of UWC were statistically significant; patients with positive findings were found to have the highest rate of disease progression, and those with negative findings experienced the lowest (P < 0.04). CONCLUSIONS: Both monitoring with UWC and urethrectomy might benefit selected individuals, but neither method appeared to have a statistically significant effect on disease progression in a nonrandomized group of patients. A positive UWC was associated with a high likelihood of disease progression and could justify more intensive follow-up for progressive disease at other sites.	bladder
Fluid intake and risk of bladder and other cancers.	There are appreciable differences in total fluid intake at the individual and population level, and substantial difficulties in obtaining valid measures of fluid intake. Epidemiological studies have examined the association between fluid intake and different types of cancer. For bladder cancer, fluid consumption has been associated with a moderate increase of risk in some studies, including a multicentric case-control study from the United States, based on about 3000 cases, with a decrease in others, including the Health Professional Follow-up study, or with no material association. The evidence, therefore, is far from consistent. Sources and components of fluids were also different across different types studies. From a biological point of view, a decreased fluid intake could result in a greater concentration of carcinogens in the urine or in a prolonged time of contact with the bladder mucosa because of less frequent micturition. Carcinogenic or anticarcinogenic components of various beverages excreted in the urine may also play a role in the process. It has been suggested that fluid consumption has a favorable effect on colorectal cancer risk. Fluid intake may reduce colon cancer risk by decreasing bowel transit time and reducing mucosal contact with carcinogens. Low fluid intake may also compromise cellular concentration, affect enzyme activity in metabolic regulation, and inhibit carcinogen removal. However, epidemiological data are inadequate for evaluation. Data are sparse and inconsistent for other neoplasms, including breast cancer. The fluid constituent of foods, confounding, interactions and possible influences of specific types of beverages should be investigated further. In conclusion therefore the association between total fluid intake and cancer risk remains still open to debate.	bladder
Evaluation and follow-up strategies for superficial bladder cancer.	"Superficial bladder cancer comprises the majority of bladder tumors presenting today. Although the word ""superficial"" connotes a benign behaving curable disease, it is clear from long-term observations of the natural history of the disease that there are two discrete entities of superficial bladder cancer, one a low-grade innocuous tumor and the other a high-grade potentially lethal tumor. These two entities vary in their histologic appearance, risk of tumor recurrence, pattern of recurrence, and risk of tumor progression. Although work on prognostic markers is promising, currently none are sufficiently reliable; therefore, clinical factors are used to identify patients with a higher risk of tumor recurrence or progression. These include the tumor stage, tumor grade, number of tumors (multifocality), presence of associated carcinoma in situ, and initial response to therapy. Surveillance schedules are individualized based on the risks for recurrence and progression. High-risk patients who undergo successful treatment of their bladder tumor initially recur more commonly in the bladder, but have a progressive risk over time of extravesical recurrences necessitating lifelong surveillance of the bladder, urethra, prostate, and upper tracts. Patients who are refractory to conservative management with intravesical therapy and TUR should be apprised of the risks for further conservative treatment and consider early radical cystectomy in an attempt to improve long-term survival. The advent and long-term success of orthotopic continent diversions has made the decision for early radical cystectomy more palatable to both the patient and physician."	bladder
The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion.	OBJECTIVES: To investigate the role of the phosphatidylinositol (PI)-3 kinase pathway in the invasion of bladder cancer cell lines, and to assess the activation of this pathway in primary human bladder tumours. MATERIALS AND METHODS: Human bladder cancer cells were treated with pathway specific inhibitors or were transfected with PI-3 kinase pathway components. The invasion of cultured bladder cancer cells was analysed by an invasion assay. Bladder cancer cells lines and primary human bladder tumours were analysed for pathway activation by western blotting. RESULTS: A specific inhibitor of PI-3 kinase enzyme activity, Ly294002, potently suppressed the invasive properties of three highly invasive bladder tumour cell lines. Restoration of the PTEN gene to invasive UM-UC-3 bladder tumour cells or expression of a dominant-negative version of the PI-3 kinase target, Akt, also potently inhibited invasion, indicating a central role for the PI-3 kinase/Akt pathway in this process. In addition, 55% of primary tumours from patients with bladder cancer had markedly high levels of phosphorylated Akt. CONCLUSION: Pharmacological or biochemical inhibition of the PI-3 kinase pathway drastically reduced the invasive capacity of bladder cancer cell lines; over half of primary human bladder tumours had high Akt phosphorylation, suggesting that the aberrant activation of this pathway may contribute to the invasion of a significant subset of bladder cancers.	bladder
Rhabdomyosarcoma of the bladder, prostate or vagina: the role of surgery.	OBJECTIVE: To retrospectively analyse the outcome of children with rhabdomyosarcoma (RMS) of the bladder, prostate or vagina who were treated with chemotherapy, with or without radical surgery or additional radiotherapy, at our institution since 1968. PATIENTS AND METHODS: From a total of 107 children with RMS seen between 1968 and December 2001, 22 (mean age 5.9, range 0.5-18) had RMS of bladder/prostate or vagina. Twenty of the patients received primary polychemotherapy (vincristine, actinomycin D, cyclophosphamide, adriamycin, and more recently including etoposide and ifosfamide), two had primary surgery and seven had additional radiotherapy. Fourteen patients had radical cystoprostatectomy, with continent cutaneous urinary diversion with an ileocaecal pouch in seven, in one each a transverse colonic pouch, orthotopic ileocaecal bladder substitution, a rectal reservoir and rectosigmoid pouch and a colonic conduit diversion in two patients. RESULTS: After a mean (range) follow-up of 8.6 (1.0-26) years, 17 patients had no evidence of disease. Five patients presenting initially with advanced tumour stages died from progressive RMS. Two patients with a continent urinary diversion required ureteric reimplantation for stenosis. In two patients severe bladder contraction after radiotherapy required bladder augmentation. CONCLUSION: Primary chemotherapy followed by radical surgery of RMS of the prostate and/or bladder allows complete tumour resection in most cases, and yields excellent cure rates.	bladder
Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: a potential therapeutic regime for bladder cancer immunotherapy.	Intravesical bacillus Calmette-Guerin (BCG) is a treatment for transitional cell carcinoma (TCC) and carcinoma in situ (cis) of the urinary bladder, but some patients remain refractory. The mechanism of cancer clearance is not known, but T cells are thought to play a contributory role. Tissue dendritic cells (DCs) are known to initiate antigen-specific immune responses following activation of receptors, which recognise molecular patterns on the surface of microorganisms. A family of these receptors, the toll-like receptors (TLRs), are also crucial for activating DC to produce cytokines that polarise the T-cell response towards a T helper (Th)1 or Th2 phenotype. This study compared the potential of intact BCG to activate DC with that of the defined TLR4 ligand lipopolysaccharide (LPS) and the TLR9 ligand CpG-oligonucleotide. It was found that all three stimuli efficiently activated normal DC, but cells expressing a mutant TLR4 responded poorly to stimulation with LPS. Importantly, stimulation with BCG induced both IL-12 and IL-10, suggesting subsequent development of a poorly focused T-cell immune response containing both Th1 and Th2 immune function. By contrast, LPS- and CpG-oligonucleotides induced only IL-12, indicating the potential to produce a Th1 response, which is likely to clear cancer most efficiently. Given the toxicity of LPS, our data suggest that CpG-oligonucleotides may be beneficial for intravesical therapy of bladder cancer.	bladder
Condyloma acuminatum-like lesion of the urinary bladder progressing to invasive spindle cell carcinoma.	Condyloma acuminata of the urinary bladder is a rare finding, particularly in the absence of similar lesions of the external genitalia. We present a case in which an isolated condyloma acuminatum-like lesion rapidly progressed to a poorly differentiated spindle cell carcinoma, underlying the need for careful endoscopic follow-up of patients with such lesions.	bladder
Papillary clusters as a diagnostic pitfall in urinary cytology of pseudosarcomatous fibromyxoid tumor of the bladder. A case report.	BACKGROUND: Pseudosarcomatous fibromyxoid tumor (PFT) of the urinary bladder is an uncommon benign lesion that can involve any site in the bladder. Cellular features of PFT of the bladder are exceedingly rare. We describe the urinary cytology in a PFT patient who displayed numerous papillary fragments that suggested a malignant tumor. CASE: A 52-year-old man was seen at the hospital for evaluation of gross hematuria. At cystoscopy, the urologist observed a 3-cm, smooth, polypoid and ulcerated mass extending from the trigone to the bladder neck. Urinary cytology showed many papillary clusters with irregular nuclear margins in the bloody cell background. No spindle cells were noted. Cytology was interpreted as papillary growth, factor transitional cell carcinoma, grade 2-3. A laparotomy with partial resection of the urinary bladder was carried out, and histologically the tumor was composed of spindle, stellate, fibroblastic cells embedded in myxoid stroma with little collagen. Immunohistochemical and ultrastructural studies revealed the fibroblastic nature of the lesion. The final diagnosis was PFT of the bladder on the basis of histologic examination of the resected material. CONCLUSION: Papillary fragments are a diagnostic pitfall in urinary cytology of PFT lesions.	bladder